X-103274227-G-A

Variant names:

• chrX-103274227-G-A
• rs1925509713
• NM_001012979.3:c.337C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001012979.3(TCEAL5):​c.337C>T​(p.Pro113Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: TCEAL5 NM_001012979.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.04

Genes affected

TCEAL5 (HGNC:22282): (transcription elongation factor A like 5) This gene, which is located on the X chromosome, encodes a protein which contains a BEX (brain expressed X-liked like family) domain. This domain is found in proteins encoded by the TCEAL elongation factor (transcription elongation factor A (SII)-like) gene family also located on the X chromosome. The coding region for this gene is located entirely in the terminal exon. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37742284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL5	NM_001012979.3	c.337C>T	p.Pro113Ser	missense_variant	Exon 3 of 3	ENST00000372680.2	NP_001012997.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCEAL5	ENST00000372680.2	c.337C>T	p.Pro113Ser	missense_variant	Exon 3 of 3	1	NM_001012979.3	ENSP00000361765.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.337C>T (p.P113S) alteration is located in exon 3 (coding exon 1) of the TCEAL5 gene. This alteration results from a C to T substitution at nucleotide position 337, causing the proline (P) at amino acid position 113 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.045	T
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	M
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.14
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.12	T
Polyphen		1.0	D
Vest4		0.32
MutPred		0.54		Gain of phosphorylation at P113 (P = 0.0028);
MVP		0.45
MPC		1.5
ClinPred		0.98	D
GERP RS		1.9
Varity_R		0.44
gMVP		0.050

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1925509713; hg19: chrX-102529155;